By Eve Bender
September 19, 2019
Article In Brief
A new study reports that the odds of having multiple sclerosis (MS) were lower in patients with a recorded vaccination in the five years before diagnosis compared with patients with no autoimmune disease. Independent experts said the findings support evidence that vaccination does not increase MS risk but they questioned whether vaccines lower MS risk.
Vaccines are not a risk factor for multiple sclerosis (MS) and were associated with a lower risk of MS, according to the findings of a large, population-based study reported in the July 30 online issue of Neurology.
“The published studies on vaccination and MS onset are conflicting,” corresponding author Bernhard Hemmer, MD, professor of neurology at the Technical University of Munich, told Neurology Today in an interview. “Early studies reported an association between MS and vaccines, while later studies did not,” he said.
Study Design, Findings
To better understand the association, Dr. Hemmer and colleagues conducted a retrospective analysis of ambulatory claims data from more than 220,000 participants held by the Bavarian Association of Statutory Health Insurance Physicians, which represents 85 percent of the Bavarian population. The data captured health insurance claims of patients aged 70 and younger from the years 2005-2017.
The researchers examined claims data on 12,260 patients who received a first diagnosis of MS in 2010 or later. Researchers then looked at vaccination rates for a variety of conditions in the five years preceding the first diagnosis, including tick-borne encephalitis virus, HPV, pneumococci, meningococci, influenza virus, hepatitis A, hepatitis B, MMR and varicella-zoster viruses, and others.
In addition to reviewing claims data from those who developed MS, Dr. Hemmer and his colleagues looked at data from three control groups—those diagnosed with Crohn’s disease (n=19,296), psoriasis (n=112,292), and individuals with no history of autoimmune disease (n=79,185).
The researchers found that the odds of having MS were lower in patients with a recorded vaccination in the five years before diagnosis compared with patients with no autoimmune disease (OR=0.870, p<0.001), patients with Crohn’s disease (OR=0.919, p<0.001), and participants with psoriasis (OR=0.973, p=0.177).
Lower odds were most pronounced for flu vaccines and those for tick-borne encephalitis. In addition, there were low rates of vaccination during the months before diagnosis, which, the authors wrote, “argues against a major role of vaccination in the induction of MS relapses.”
But what could account for the decreased rates of the vaccinations, especially in the months leading up to vaccination? Dr. Hemmer referred to an “MS prodrome,” noted in previous studies, in which prior to diagnosis, some patients could experience an awareness of their disease and may alter their behavior in accordance with that experience.
While the data show a negative association of vaccines with MS, the authors noted that “the data alone do not allow for any conclusion regarding a possible protective effect of vaccinations regarding the development of MS.”
He added that his future research will extend the observational period from five to 10 years before diagnosis to continue the comparison between MS and control groups in respect to vaccination risk.
The authors noted that study limitations include the subjective definition of the MS cohort and the data source itself, which could be subject to data entry errors.
Commenting on the study, Anne Langer-Gould, MD, PhD, regional lead for clinical and translational neuroscience at Southern California Permanente Medical Group/Kaiser Permanente, said “it was notable that the researchers found no increased risk of MS following any vaccinations in comparison to multiple control groups, and sensitivity analyses also support this conclusion.
“It is, however, extremely unlikely that vaccines decrease the risk of MS as the authors report,” she said, adding that an important study limitation “makes the finding of decreased odds of MS following vaccinations more likely a spurious finding.” This includes the fact that the analysis did not account for differences in health care utilization among cases and controls, she said.
“This is important in vaccine studies as vaccines are usually administered when a patient seeks care for another reason. Why were the controls more likely to have been vaccinated? Were they seeking care more often? If so, for what?”
She also pointed out that using a marker of diagnosis for MS may not be realistic or accurate in capturing data for these patients. “The delay between symptom onset and diagnosis is about three to five years, depending upon the symptoms and health care system,” she noted. “A better approach is to identify the code for a neurological symptom such as dizziness, numbness, or weakness by any provider since these patients rarely see a neurologist first.”
Alberto Ascherio, MD, PhD, agreed that the findings further strengthened the evidence that vaccination does not increase MS risk. “The study stands out for its large sample size, which allowed examination of specific vaccines and assessment of potential biases in sensitivity analyses,” said Dr. Ascherio, professor of medicine, epidemiology and nutrition at Harvard Medical School.
He noted that despite the suggestion that some vaccines may even reduce MS risk should be interpreted cautiously, “these results are strongly reassuring and good news for public health.”
Kassandra Munger, ScD, a research scientist at the Harvard T.H. Chan School of Public Health who has done research on vaccinations, also agreed that the study’s findings, “coming from a large, population-based dataset, showing no increase in MS risk with vaccination, lend more weight to prior study findings showing that vaccines do not contribute to the development of MS.”
“The use of population-based administrative data covering approximately 85 percent of the Bavarian population is a strength of this study, and it is plausible the results are generalizable to other similar populations,” Dr. Munger said. “The use of administrative data in observational studies of multiple sclerosis has been growing in recent years and similar studies on vaccination and MS risk in other populations are needed to confirm these findings.”
Dr. Hemmer has served on scientific advisory boards for Novartis and as a DMSC member for AllergyCare and TG Therapeutics; he or his institution have received speaker honoraria from Desitin; and he holds part of two patents, one for the detection of antibodies against KIR4.1 in a subpopulation of patients with MS and one for genetic determinants of neutralizing antibodies to interferon-β.